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Positron emission tomography tracer [68Ga]NODAGA-Exendin-4 detects glucagon-like peptide-1 receptor expression in mouse atherosclerotic vascular lesions

List of Authors: Mia Ståhle, Sanna Hellberg, Jenni Virta, Heidi Liljenbäck, Olli Metsälä, Matti Jauhiainen, Pekka Saukko, Seppo Ylä-Herttuala, Pirjo Nuutila, Juhani Knuuti, Antti Saraste, Anne Roivainen
Publication year: 2017
Journal: Atherosclerosis
Journal acronym: Atherosclerosis
Volume number: 263


Aim: Pharmacological activation of glucagon-like peptide-1 receptor
(GLP-1R) signalling attenuates the development of atherosclerosis and vascular
inflammation in experimental models. We
evaluated whether positron emission tomography (PET) tracer [68Ga]NODAGA-Exendin-4
enables detection of GLP-1R expression in the aorta of atherosclerotic and
diabetic mice.


Methods: Eight atherosclerotic low density lipoprotein receptor deficient
mice expressing only apolipoprotein B100 (LDLR-/-ApoB100/100), eight atherosclerotic and diabetic mice overexpressing
insulin-like growth factor II (IGF-II/LDLR-/-ApoB100/100),
and ten healthy C57BL/6N mice were injected with 20±2 MBq of [68Ga]NODAGA-Exendin-4
and sacrificed 60 minutes later. Aorta and other tissues were excised and measured
for total radioactivity by a gamma counter. The aorta was cut into cryosections
for autoradiography, histology and immunohistochemistry of GLP-1R and Mac-3


Results: Aortas of both LDLR-/-ApoB100/100 and
IGF-II/LDLR-/-ApoB100/100 mice contained macrophage-rich
atherosclerotic plaques and diabetic mice demonstrated hyperglycemia and glucose
intolerance. Compared with healthy mice, gammacounting revealed increased
(p<0.05) [68Ga]NODAGA-Exendin-4 uptake in aortas of both LDLR-/-ApoB100/100
and diabetic- IGF-II/LDLR-/-ApoB100/100
mice (SUV 0.15±0.05 vs. 0.23±0.06 and 0.22±0.05, respectively). By autoradiography,
tracer uptake was focally increased (p<0.001) in macrophage-rich, GLP-1R-positive
lesion areas compared with corresponding healthy vessel wall. Plaque [68Ga]NODAGA-Exendin-4
uptake was significantly reduced after pre-treatment with an unlabelled GLP-1
peptide (plaque-to-vessel wall ratio 1.6±0.1 vs. 1.4±0.1, p=0.003).


Conclusions: Our results provide
evidence that [68Ga]NODAGA-Exendin-4
detects increased GLP-1R expression in the atherosclerotic aorta of both
non-diabetic and diabetic mice. Molecular imaging of GLP-1R has translational
relevance studying the vascular actions of GLP-1 in atherosclerotic
cardiovascular disease.

Last updated on 2019-12-06 at 16:01